What is the treatment for a patient with iron deficiency anemia, characterized by low iron levels, elevated Total Iron-Binding Capacity (TIBC), and low iron saturation?

Treatment of Iron Deficiency with Serum Iron 34 µg/dL, TIBC 243 µg/dL, Transferrin Saturation 14%

Start oral iron supplementation immediately with ferrous sulfate 150-200 mg elemental iron daily, as this patient has confirmed iron deficiency anemia based on transferrin saturation <16%. 1

Diagnostic Confirmation

Your patient's laboratory values confirm iron deficiency:

• Transferrin saturation of 14% is below the 16% threshold that indicates insufficient iron available for erythropoiesis and confirms absolute iron deficiency 2, 1
• TIBC of 243 mg/dL is at the lower end of normal (normal range 250-370 mg/dL), which can occur in early iron deficiency 2, 1
• Serum iron of 34 µg/dL is significantly below the normal range of 50-175 µg/dL, confirming depleted circulating iron 2

Critical Next Step: Measure Serum Ferritin Immediately

You must obtain a serum ferritin level to quantify iron stores, as this is essential for complete diagnosis and monitoring treatment response 2, 1. Ferritin <15 mcg/L indicates absolute iron deficiency, while <30 mcg/L generally indicates depleted stores 1. If ferritin is 30-100 mcg/L with inflammation present, this still represents iron deficiency requiring treatment 1.

Initial Treatment Protocol

Oral Iron Supplementation (First-Line)

• Prescribe ferrous sulfate 324 mg tablets (65 mg elemental iron) 2-3 times daily for a total of 150-200 mg elemental iron per day 2, 1, 3
• Consider alternate-day dosing rather than daily dosing, as recent evidence shows better iron absorption and fewer adverse effects with this approach 2
• Take on an empty stomach when possible for optimal absorption; if not tolerated, taking with meals (especially with meat protein) is acceptable 2
• Add 500 mg vitamin C with each dose to enhance absorption even when taken with food 2

Common Side Effects and Management

Gastrointestinal side effects (nausea, abdominal pain, constipation, diarrhea) are common and represent the main reason for treatment failure 2, 4. If ferrous sulfate is not tolerated, consider switching to ferrous fumarate, ferrous gluconate, or ferrous bisglycinate, though no formulation has proven superior in effectiveness 2.

Investigating the Underlying Cause

All adults with confirmed iron deficiency require investigation for gastrointestinal blood loss, except premenopausal women with documented menorrhagia 1:

• Bidirectional endoscopy (upper and lower) is mandatory to exclude gastrointestinal malignancy 1
• Test for Helicobacter pylori infection, as this can impair iron absorption 2, 5
• Screen for celiac disease with serological testing, as this causes malabsorption 2
• Evaluate dietary iron intake and menstrual blood losses in premenopausal women 2
• Perform stool guaiac testing for occult blood 1

Critical Pitfall to Avoid

Do not assume menstruation is the cause in women >40 years or those with severe anemia without excluding GI pathology 1. Even premenopausal women with menorrhagia may have concurrent gastrointestinal disease.

When to Escalate to Intravenous Iron

Consider IV iron therapy if 2, 1:

• No response to oral iron after 4-6 weeks (65% of oral iron non-responders respond to IV iron, compared to only 21% who respond to continued oral therapy) 1
• Severe iron deficiency requiring rapid repletion (e.g., before elective surgery) 2
• Malabsorption conditions (celiac disease, inflammatory bowel disease with active inflammation, post-gastric surgery) 2
• Intolerable gastrointestinal side effects from oral preparations 2, 4
• Ongoing blood loss exceeding intestinal absorption capacity (e.g., angiodysplasia) 4

IV Iron Formulations

Ferric carboxymaltose is the best-studied option, allowing rapid administration of large single doses (up to 1000 mg elemental iron) over 15 minutes 2. Other options include iron sucrose, ferric gluconate, and low molecular weight iron dextran 2. Avoid high molecular weight iron dextran due to higher risk of serious reactions 2.

Monitoring Treatment Response

• Recheck complete blood count, iron studies, and ferritin after 8-10 weeks of treatment, not earlier, as ferritin levels are falsely elevated immediately after IV iron 2
• Target ferritin >30 mcg/L and transferrin saturation >20% to confirm adequate iron store repletion 1
• Hemoglobin should increase by 1-2 g/dL after 3-4 weeks of adequate oral iron therapy 6

Non-Response Indicates

• Malabsorption (celiac disease, atrophic gastritis, H. pylori infection) 2, 5
• Non-compliance with oral therapy 1
• Ongoing blood loss exceeding absorption 4
• Inflammation with hepcidin upregulation blocking iron absorption 2, 1
• Incorrect diagnosis (consider thalassemia trait, anemia of chronic disease, or combined deficiencies) 1

Additional Workup to Consider

• Check inflammatory markers (CRP, ESR) to interpret ferritin accurately, as ferritin is an acute phase reactant 2, 1
• Assess renal function to evaluate for chronic kidney disease as a contributing factor 1
• Check thyroid function as hypothyroidism can contribute to anemia 1
• Perform hemoglobin electrophoresis if microcytosis persists with normal iron studies to exclude thalassemia 1